White Matter Microstructural Damage on Diffusion Tensor Imaging in Cerebral Small Vessel Disease

Abstract

C erebral small vessel disease (SVD) is a major health problem for its contribution to ≈45% of dementias, and about a fifth of all strokes worldwide, representing one of the most important causes of disabilities.1 The term SVD refers to a group of pathological processes with various etiologies that affect the small arteries, arterioles, venules, and capillaries of the brain. The most common forms are age-and hypertensionrelated SVD and cerebral amyloid angiopathy (CAA).2 Vessel wall changes may lead to both ischemic and hemorrhagic consequences: (1) a state of chronic hypoperfusion or vascular dysfunction responsible for incomplete infarction, 3,4 (2) acute focal necrosis (lacunar infarct), or (3) vessel rupture manifesting as hemorrhagic SVD. The clinical consequences of SVD are various and mainly consist of cognitive, mood, and motor dysfunctions leading to functional disability in the late stages of the disease.Magnetic resonance imaging (MRI) has become crucial in the diagnosis of SVD enabling the evaluation of the disease progression both in the clinical and research settings. However, correlations between clinical features of SVD and conventional MRI measures have been partially discordant. Some authors suggested that the cumulative effect of SVD lesions, rather than the individual lesions themselves determines the clinical impact, 5 whereas others suggested that the presence and severity of alterations nonvisible on conventional MRI might also be an explanation. 6 In the past decade, diffusion tensor imaging (DTI) has been increasingly used for the evaluation of SVD patients because it is sensitive to tissue damage and can show abnormalities in both areas of white matter hyperintensities (WMH) and in normal appearing WM (NAWM). Despite the high sensitivity in detecting cerebral damage, DTI has a low specificity in detecting the underlying cause. In fact, we can only infer that DTI changes reflect a loss of WM integrity because of damage to structures that restrict molecular movement along the primary axis of the axons, such as axonal cell membranes, myelin sheaths, and neurofilaments. Growing evidences indicate definite structural vascular abnormalities associated with WMH, strengthening the argument that WMH have a vascular pathogenesis.7 DTI is suited to study cortical disconnection because it provides indices of microstructural integrity within interconnected neural networks. Most DTI studies evaluated WM microstructural damage in aging, Alzheimer disease and mild cognitive impairment patients, but recently, studies in SVD patients have documented a significant association between WM microstructural damage and clinical features, providing new insight in the biological basis of this condition. 8-10The aim of this review is to analyze the evidence of the role of WM microstructural damage beyond the standard structural MRI sequences, evaluated with DTI, in the clinical consequences of cerebral SVD. Although some definitions have been proposed, 11 it is explicitly not our intention to clinically define...

Integrity of normal-appearing white matter and functional outcomes after acute ischemic stroke

“…6,7,21 DTI-based techniques, which are predicated on the quantification of the randomness of water molecule diffusion, are informative on the microstructural integrity of WM. 9,26,27 With respect to NAWM, several studies have used a DTI-based approach to emphasize that the detection of microstructural injury of NAWM precedes the genesis of overt WMH. 6,28 A recent study of patients with mild ischemic stroke demonstrated that MD was the most sensitive metric for distinguishing WMH from NAWM and that the accumulation of interstitial fluid is involved in WMH pathogenesis.…”

“…17 Therefore, it is reasonable to assume that DTI-based anisotropy metrics of NAWM provide insights into WM composition and, as a result, are informative of functional connectivity and overall cognitive performance. 7,27,[29][30][31] Thus, it seems intuitive that WM integrity would influence poststroke recovery. 3,4,[32][33][34][35] The exact mechanisms by which prestroke WM integrity might influence poststroke functional recovery are yet to be determined; however, data that underscore the role of structural connectivity in functional performance in general populations point in the direction of potential underlying pathology.…”

The Role of White Matter Damage in the Risk of Periprocedural Diffusion-Weighted Lesions after Carotid Artery Stenting

“…Since in the general population the prevalence of WMH is strictly associated with age, ranging from 11 to 21% in most octogenarians [27,28,29], we entered the term “age” in the multivariate model, obtaining similar results.…”

Cognitive function and cerebral small vessel disease in hypertension

“…In the Rotterdam Scan Study, which is part of the large population-based Rotterdam Study, it was shown that presence of cerebral infarcts at baseline was associated with a doubled risk of dementia and a steeper decline in global cognitive function over a mean of 3.6 years. 43 Severity of periventricular WMH and cerebral infarcts were associated with a steeper decline in cognitive function over a mean of 5.2 years. 44 In the 3-year follow-up of the LADIS study, which included subjects between 65 and 84 years with at least mild WMH, baseline WMH volume predicted cognitive decline, while baseline number of lacunes did not have an independent association with cognitive decline.…”

“…42,43 Decreased microstructural integrity of NAWM and WMH have been shown to be associated with higher blood pressure levels. 44 In addition, DTI studies showed that lower microstructural integrity in the white matter was associated with lower cognition.…”